Phase II Trial of Ixabepilone Plus Carboplatin in Patients With Metastatic Breast Cancer: The ECLIPSE Study

Inclusion Criteria:

Male or female patients will be eligible for inclusion in this study if they meet all of
the following criteria:

1. Has measurable metastatic and or locally unresectable breast cancer with documented
HER2 negative (-) disease

2. Has at least 1 measurable lesion per RECIST criteria (lesions that can be
accurately measured in at least 1 dimension (longest diameter (LD) to be recorded) as
≥20 mm with conventional techniques (CT, MRI, X-ray) or as ≥10 mm with spiral CT
scan). Irradiated lesions cannot be used to assess response but can be used to assess
progression.

3. Has received up to 2 (0 to 2) prior chemotherapy regimens for metastatic disease with
the following conditions:

•Has had no prior treatment with ixabepilone or platinum agents

4. Has had no adjuvant chemotherapy within the 6 months prior to study, but may have
received prior anthracyclines and/or taxanes as adjuvant chemotherapy

5. 3 weeks or more have elapsed since last chemotherapy treatment and any related
toxicities have resolved to investigational product has been administered and associated toxicities must have
resolved to
6. Has an ECOG Performance Status (PS) 0-2

7. Is ≥18 years of age

8. Has a life expectancy of at least 12 weeks

9. Has laboratory values of:

White blood cell (WBC) count ≥3000 x 106/L Absolute neutrophil count (ANC) ≥1500 x
106/L Hemoglobin ≥9 g/dL Total bilirubin ≤1x upper limit of normal (ULN) AST and ALT
≤2.5 x ULN Alkaline phosphatase ≤2.5 x ULN; up to 5xULN if elevation is due to bone
disease Serum creatinine ≤1.5 mg/dL Calculated creatinine clearance >50 mL/min (based
on Cockroft and Gault method [Appendix III]) Platelet count ≥100,000 x 106/L

10. If patient has had radiation therapy, it has been completed >3 weeks prior to the
start of study treatment. NOTE: Previously irradiated lesions will not be evaluable.
However, these patients will still be eligible.

11. Has a negative serum pregnancy test within 7 calendar days prior to registration
(female patients of childbearing potential [not surgically sterilized and between
menarche and 1 year postmenopause

12. If fertile, patient (male or female) has agreed to use an acceptable method of birth
control to avoid pregnancy for the duration of the study and for a period of 3 months
thereafter

13. Has signed the most recent Patient Informed Consent Form

14. Has signed a Patient Authorization Form Note: Having tissue available is not an
inclusion criterion in this study; however, available tissue will be collected (see
Section 8) if possible.

Exclusion Criteria:

A patient will be excluded from this study if he or she meets any of the following
criteria:

1. Had prior treatment with ixabepilone or other epothilones

2. Had prior radiation to ≥30% of major bone marrow containing areas (pelvis, lumbar
spine)

3. Has ER+ and/or PR+ disease that has not progressed on hormone therapy, unless the
patient has life-threatening or rapidly progressing visceral disease

4. Has HER2+ disease (IHC staining of 3+ [uniform, intense membrane staining of >30% of
invasive tumor cells]), a FISH result of more than 6 HER2 gene copies per nucleus or
a FISH ratio (HER2 gene signals to chromosome 17 signals of >2.2)

5. Has only lytic bone disease or nonmeasurable disease only

6. Has a known, prior, severe (NCI CTCAE Grade 3-4) history of hypersensitivity reaction
to a drug formulated in Cremophor®EL (polyoxyethylated castor oil) or has history of
severe allergic reactions to cisplatin or other platinum-containing compounds

7. Has been treated previously with a platinum-containing agent

8. Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy.
Washout periods for these prior therapies are specified in Section 5.

9. Is receiving concurrent investigational therapy or has received such therapy within
the 30 days prior to dosing Day 1

10. Has neuropathy (motor or sensory) >Grade 1

11. Has evidence of CNS involvement requiring radiation or steroid treatment. Patients
with stable brain metastases who are off steroids at least 2 weeks are eligible.

12. Has a serious uncontrolled intercurrent medical or psychiatric illness, including
serious infection

13. Has clinically relevant coagulopathy either secondary to hepatic dysfunction or an
underlying condition requiring therapeutic anticoagulation (specifically, A-fib,
history of DVT). A daily aspirin or Plavix for CAD are permitted.

14. Has a history of other malignancy within the last 5 years (except cured basal cell
carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the
diagnosis or assessment of any of the study drugs

15. Is a pregnant or breast feeding woman

16. Is unable to comply with the requirements of the study